Here is the main discussion of "words used as words" in The Chicago Manual of Style, 16th edition (2010):
7.58 Words and phrases used as words. When a word or term is not used functionally but is referred to as the word or term itself, it is either italicized or enclosed in quotation marks. ...
[Example:] The term critical mass is more often used metaphorically than literally.
[Example:] What is meant by neurobotics?
Chicago's discussion indicates that when a word is being used as a word in the narrow sense, the sentence would continue to convey the writer's intended meaning if you added "the word" in front of the word being used as a word. Thus, in Chicago's second example above, it would make perfect sense to insert "the word" before neurobotics:
What is meant by the word neurobotics?
Pretty straightforward so far, right? Now let's apply it to the first three examples that you raise. First:
Humans, naturally, prefer simple over complex.
If the words simple and complex were being used as words, it would make sense to say this:
Humans, naturally, prefer the word simple over the word complex.
But that doesn't sound right. There is no reason to suppose that humans naturally prefer the word simple over the word complex insofar as they are merely words. Why should they?
So what's going on with the original sentence? Well, I'd say that the intention of that original sentence is to claim that people prefer simple things over complex things. That is, the implied (but absent) element in the original sentence isn't "the word" (twice) but "things" (twice):
Humans, naturally, prefer simple things over complex things.
This version of the sentence makes sense—and it establishes pretty clearly that simple and complex weren't being used as words in the original sentence. For that reason, Chicago wouldn't endorse italicizing them.
Now let's look at the second example in your question:
I prefer red over green.
If red and green were words used as words, the sentence would still express the writer's original meaning if we reworded it as follows:
I prefer the word red over the word green.
But it seems far more likely that the writer intended to use the words as colors, not as words. That is:
I prefer the color red over the color green.
And if that was the writer's intention, red and green in the original sentence were not being used as words.
Your third example raises a somewhat more challenging issue: how do we handle words used as concepts? Here is the example:
The scientific distinction between simple and complex has long been blurred.
If we apply our word-used-as-word test to this form of the sentence, the result isn't very satisfactory:
The scientific distinction between the word simple and the word complex has long been blurred.
The problem is that the blurry scientific distinction isn't between two words—one six letters long and one seven letters long. It's between two problematic concepts:
The scientific distinction between the concept of simple and the concept of complex has long been blurred.
or two fundamental meanings:
The scientific distinction between the fundamental meaning of simple and the fundamental meaning of complex has long been blurred.
In my view, simple in the phrase "the concept of simple" isn't a word used as a word; rather, it's a word used to convey a particular idea that we've given the name simple to. I would therefore not italicize simple and complex in that form of the sentence. In fact, we might very well interpret the scientific dispute in a vulgarly materialistic way, as follows:
The scientific distinction between simple things and complex things has long been blurred.
In that case, we're clearly not dealing with the words simple and complex used as words.
But the version of the sentence involving "the meaning of simple" seems different. There, we are just one crucial interpretive step from fully satisfying the word-used-as-word condition—and once again that step consists of adding "the word" to the revised sentence (twice):
The scientific distinction between the fundamental meaning of the word simple and the fundamental meaning of the word complex has long been blurred.
What do you know—we're back to making a statement about the meaning of two words used as words!
These results demonstrate that how you interpret a bare-bones sentence can sometimes make the difference between whether you conclude that certain words in it are being used as words (in the Chicago sense) or not.